Progressive anastomotic stenosis is a significant cause of failure of small diameter synthetic grafts after arterial reconstruction. The mechanisms by which stenosis develops are not known but may relate to abnormal proliferation of vascular smooth muscle cells. The objective of this proposal is to define the role of endothelial (EC) and smooth muscle (SMC) proliferation in the formation of anastomotic stenoses in a baboon model of graft failure. In particular we shall investigate the possibility that this process is the result of: 1) initial SMC and EC migration and proliferation to cover the luminal surface of the graft; 2) persistent intimal SMKC proliferation at the anastomosis resulting in graft stenosis; 3) recurrent endothelia injury in regions of established anastomotic stenosis leading to accumulation of thrombus and accelerated SMC growth. The proposed studies will utilize baboon models of graft failure and arterial stenosis, light and electron microscopy, autoradiography, morphometry, and immunohistochemistry.